Vemurafenib for the treatment of locally advanced or metastatic BRAF V600
mutation-positive malignant melanoma: a NICE single technology appraisal.
Author(s): Beale S(1), Dickson R, Bagust A, Blundell M, Dundar Y, Boland A, Marshall E,
Plummer R, Proudlove C.
Affiliation(s): Author information:
(1)Liverpool Reviews and Implementation Group, University of Liverpool, Whelan
Building, Brownlow Hill, Liverpool, L69 3GB, UK, s.beale@liv.ac.uk.
Publication date & source: 2013, Pharmacoeconomics. , 31(12):1121-9
Vemurafenib is an oral BRAF inhibitor licenced for the treatment of locally
advanced or metastatic BRAF V600-mutation positive malignant melanoma. The
manufacturer of vemurafenib, Roche Products Limited, was invited by the National
Institute for Health and Care Excellence (NICE) to submit evidence of the drug's
clinical- and cost-effectiveness for its licenced indication, to inform the
Institute's Single Technology Appraisal (STA) process. The Liverpool Reviews and
Implementation Group (LRiG) at the University of Liverpool was commissioned to
act as the Evidence Review Group (ERG) for this appraisal. This article
summarises the ERG's review of the evidence submitted by the manufacturer and
also includes a summary of the NICE Appraisal Committee (AC) decision. The ERG
reviewed the clinical- and cost-effectiveness evidence in accordance with the
decision problem defined by NICE. The ERG's analysis of the submitted economic
model assessed the appropriateness of the approach taken by the manufacturer in
modelling the decision problem. It also included an assessment of the reliability
of model implementation and the extent of conformity to published standards and
prevailing norms of practice within the health economics modelling community.
Particular attention was paid to issues likely to impact substantially on the
base-case cost-effectiveness results. The clinical evidence was derived from BRIM
3 (BRAF Inhibitor in Melanoma 3), a well-designed, multi-centre, multi-national,
phase III, randomised controlled trial (RCT). Clinical outcome results from the
October 2011 data cut showed that median overall survival for patients treated
with vemurafenib was 13.2 months compared with 9.6 months for those treated with
dacarbazine. The ERG's main concern with the trial was the potential for
confounding because of the early introduction of the crossover from the
comparator drug to vemurafenib or another BRAF inhibitor. The submitted
incremental cost-effectiveness ratio (ICER) was considered above the NICE
threshold, even when end-of-life criteria were taken into account. The ERG
questioned the submitted economic model on a number of grounds, particularly the
approach used to project trial results. After the ERG had made appropriate
corrections to the model and employed an alternative form of projective
modelling, the ICER per quality-adjusted life year more than doubled. Additional
evidence was submitted by the manufacturer for consideration at a second AC
meeting and at their third meeting the AC concluded that vemurafenib could be
recommended as first-line maintenance treatment for patients with locally
advanced or metastatic BRAF V600 mutation-positive malignant melanoma.
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